This Core is a centralized facility that produces transgenic mice and generates mice from embryonic stem (ES) with alterations generated by gene targeting. Transgenic mice can be used for many applications, including the study of tissue specific gene expression, production of animal models of human disease, and for testing the efficacy of gene constructs for gene therapy. Transgenic mice can be used for many applications, including the study of tissue specific gene expression, production of animal models of human disease, and for testing the efficacy if gene constructs for gene therapy. ES cell technology can be used to establish animal models of recessive genetic disease and to characterize functional effects of gene loss and subtle changes in gene. Other services include cryopreservation and retrieval of mouse lines and derivation of pathogen free mice from conventional mouse colonies. The Core maintains specialized reagents for transgenic and gene targeting research. The availability of a Transgenic Core on site obviates the need for individual researchers to purchase costly equipment and invest personnel time in training in micromanipulation techniques. Consultation on all aspects of transgenic and ES cell research is provided, from the design of DNA constructs to mouse husbandry. Production of Transgenic Mice: We deliver an average pf ten transgenic founder mice and guarantee that at least three founders will be produced for each DNA construct submitted to the Core. Production of Gene Targeted ES Cells: The Core will electroporate totipotent ES cells with targeting vectors, select ES cell clones, and provide Center Members with DNA from the clones for genetic screening. Production of ES Cell-Mouse Chimeras: ES cell clones carrying the desired genetic mutation will be microinjected into mouse blastocysts which are surgically transferred to foster mothers to produce chimeras. Projected annual usage of the Core by Center members is 30 orders for transgenic mice, 30 orders for ES cell-mouse chimeras, and 10 orders for production of gene targeted ES cells. This represents two-thirds of the Core's capacity and is consistent with past usage by Center members, who have constituted the majority of Core use. The recharge rate for Cancer Center members will be discounted by 25% for transgenic mouse production, by 30% for producing targeted ES cells, and by 25% for ES cell-mouse chimera production.